This proposal is predicated on two properties of human-murine somatic cell hybrids: the gradual loss of human chromosomes, allowing for clonal isolation of hybrids with one or few human chromosomes; and the codominant expression of constitutive cell surface antigens of each parent on the cell surface. Hybrid cells containing one or several human chromosomes will be injected into mice syngeneic to the mouse parental cell, and the antisera analyzed on panels of target cells designated so that reactions specific to human cell surface molecules will be demonstrated. Immunoprecipitation and electrophoretic analysis will be used to discriminate the number of antigenic molecules coded for by a particular chromosome and these antisera will be used for biochemical and functional analysis of the molecules themselves. Humoral reactivity to tumorigenic (in the nude mouse) hybrid cells derived from fusions of human tumor-derived and normal mouse cells will be analyzed to determine if tumor-associated specific antigens unique to the human parental tumor-derived cell lines and tumor cell lines of similar histologic type are expressed on these hybrids. We shall also screen these antisera for reactivity to human and/or mouse embryonic antigens which are often re-expressed on the tumor cell surface.